emale. The population was80.9% White, 8.3% Black or African American, 3.7% Asian, and 6.6% Other race. At baseline thepopulation had diabetes for an average of 7.5 years and a mean HbA1c of 8.4%. The mean eGFR atbaseline was 94.4 mL/min/1.73 m2.
The common adverse reactions were based on the pooled analyses of these studies as shown in Table 1.
Table 1: Adverse Reactions Reported in ≥2% of Subjects
Treated with 10 mg Dapagliflozin and 5 mg Saxagliptin plus
Metformin (≥1500 mg)
Adverse Reaction
Preferred Term* Frequency %
Upper respiratory tract infection* 13.6
Urinary tract infection* 5.7
Dyslipidemia* 5.1
Table 1: Adverse Reactions Reported in ≥2% of Subjects
Treated with 10 mg Dapagliflozin and 5 mg Saxagliptin plus
Metformin (≥1500 mg)
Adverse Reaction
Preferred Term* Frequency %
Headache 4.3
Diarrhea 3.7
Back pain 3.3
Genital infection* 3.0
Arthralgia 2.4
* Adverse reactions that are medically related were grouped to a single preferred
term.
Additionally, adverse reactions reported in <5% and ≥2% from the dapagliflozin development programand ≥1% more frequently compared to placebo included increased urination and discomfort withurination.
Metformin
In placebo-controlled monotherapy trials of metformin extended-release, diarrhea and nausea/vomitingwere reported in >5% of metformin-treated patients and more commonly than in placebo-treated patients(9.6% versus 2.6% for diarrhea and 6.5% versus 1.5% for nausea/vomiting). Diarrhea led todiscontinuation of study medication in 0.6% of the patients treated with metformin extended-release.
Hypoglycemia
In the pooled analysis, the incidences of hypoglycemia (defined as blood glucose <54 mg/dL regardlessof the presence or absence of symptoms) and severe hypoglycemia (events requiring assistance due toneuroglycopenia, characterized by altered mental and/or physical status) were 1% and 0.2%, respectively.
Genital Mycotic Infections
Genital mycotic infections were reported in 15 subjects (3%) treated with combination plus metformintherapy. Reported adverse reactions by frequency included vulvovaginal mycotic infection,balanoposthitis, genital fungal infection, vaginal infection, and vulvovaginitis. The majority of subjects(84.2%) who experienced genital infection adverse reactions were females.
Urinary Tract Infections
Urinary tract infections were reported in 28 subjects (5.7%) treated with combination plus metformintherapy. Reported adverse reactions by frequency included urinary tract infection, Escherichia urinarytract infection, prostatitis, and pyelonephritis. The majority of subjects (80.6%) who experienced urinarytract infection adverse reactions were females.
Volume Depletion
Dapagliflozin causes an osmotic diuresis, which may lead to reductions in intravascular volume. Eventsrelated to volume depletion (hypotension, dehydration, and hypovolemia) were reported in 2 subjects(0.4%) treated with dapagliflozin, saxagliptin and metformin combination therapy.
Impairment of Renal Function
Dapagliflozin and Saxagliptin plus Metformin
Adverse reactions related to decreased renal function were reported in 10 subjects (2.0%) treated withcombination plus metformin therapy. The reported adverse reactions included decreased glomerularfiltration rate, renal impairment, increased blood creatinine, acute ren
